New Antibody-Cytokine Fusion Proteins for the Therapy of Neuroblastoma
Abstract
To improve immunotherapy for neuroblastoma, an anti-disialoganglioside (GD2) antibody and interleukin (IL)-2 fusion protein was generated (hu14.18-IL-2) that achieved tumor regression in 16-22 percent of patients enrolled in phase II clinical trials. However, more than 90 percent of participating children experienced toxicity, and bulky tumors did not respond. I recently demonstrated that substituting IL-15 for IL-2 in a current neuroblastoma immunotherapy regimen resulted in elevated levels of cytotoxicity in mice with bulky tumors, conceivably by promoting differentiation of tumor-infiltrating NK cells and up regulation of Gzmd. IL-21, a pleiotropic cytokine that also activates NK cells, has not been broadly studied in neuroblastoma. Herein, I propose to engineer and test new antibody-cytokine fusion proteins for the treatment of neuroblastoma. Objectives/hypothesis: The objective of this grant proposal is to determine the effectiveness of two novel antibody-cytokine fusion proteins, aGD2-IL-15 and aGD2-IL-21, and compare them with hu14.18-IL-2. I hypothesize that a GD2-IL-15 and a GD2-IL-21 can cause equivalent or higher tumor regression than hu14.18- IL-2, presumably due to cytokine-specific phenotypic and transcriptomic changes in tumor-infiltrating lymphocytes (TILs).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1201584
Entities
People
- Rosa Nguyen
Organizations
- Geneva Foundation